| In the past, Dr. Maher's research group has studied how defects in ability of human cells to repair DNA damage induced by various chemical carcinogens, ultraviolet radiation, or ionizing radiation leads to permanent changes (mutations) in the primary DNA sequence of genes, including cancer-related genes (oncogenes and suppressor genes). Her group developed methods for detecting DNA damage and rates of repair at the level of the nucleotide. Presently, she and her group of researchers are investigating the mechanisms involved in carcinogen-induced mutation induction by DNA damage that blocks replication and the mechanisms by which human cells are able to continue to replicate DNA that contains such lesions. They are investigating the roles played by a series of newly-discovered DNA polymerases, such as Pol Zeta (hRev3 and hRev7), hRev1, Pol Eta, Pol Iota, and Pol Kappa etc. Such polymerases in combination with one another, are capable of replicating past fork-blocking lesions in DNA, but at the cost of making errors (mutations). Therefore, they play a causal role in the development of cancer. Dr. Maher's research group has shown that, in addition to using these error-prone polymerases to continue replicating DNA containing fork-blocking lesions, human cells can make use of an undamaged homologous copy of the blocked gene to circumvent the replication problem. The latter mechanism, designated gene conversion or homologous recombination, is essentially error-free. |
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